Kottur, Jithesh and Nair, Deepak T (2018) Pyrophosphate hydrolysis is an intrinsic and critical step of the DNA synthesis reaction. Nucleic Acids Research. ISSN 0305-1048

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Abstract

DNA synthesis by DNA polymerases (dPols) is cen- tral to duplication and maintenance of the genome in all living organisms. dPols catalyze the formation of a phosphodiester bond between the incoming de- oxynucleoside triphosphate and the terminal primer nucleotide with the release of a pyrophosphate (PPi) group. It is believed that formation of the phospho- diester bond is an endergonic reaction and PPi has to be hydrolyzed by accompanying pyrophosphatase enzymes to ensure that the free energy change of the DNA synthesis reaction is negative and it can proceed in the forward direction. The fact that DNA synthesis proceeds in vitro in the absence of py- rophosphatases represents a long-standing conun- drum regarding the thermodynamics of the DNA syn- thesis reaction. Using time-resolved crystallography, we show that hydrolysis of PPi is an intrinsic and crit- ical step of the DNA synthesis reaction catalyzed by dPols. The hydrolysis of PPi occurs after the forma- tion of the phosphodiester bond and ensures that the DNA synthesis reaction is energetically favor- able without the need for additional enzymes. Also, we observe that DNA synthesis is a two Mg2+ ion assisted stepwise associative SN2 reaction. Overall, this study provides deep temporal insight regard- ing the primary enzymatic reaction responsible for genome duplication.

Item Type:	Article
Subjects:	Biochemical and Biophysical Sciences
Depositing User:	Dr Vengadesan Krishnan
Date Deposited:	30 Aug 2018 12:06
Last Modified:	30 Aug 2018 12:06
URI:	http://rcb.sciencecentral.in/id/eprint/161

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